BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean 6 SD of 1.04 6 1.03% (Cohen's d = 1.01, p , .001) and the subcortical gray matter volume increased by 1.47 6 1.05% (d = 1.40, p , .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation r = 2.44, p , .001), while total white matter volume remained unchanged (d = 20.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and 11C-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

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The human neural correlates of social rejection have attracted significant research interest, but remain subject to vigorous debate. Specifically, it has been proposed that a matrix of brain regions overlapping with the classical pain matrix, and including the dorsal anterior cingulate cortex (dACC) and the anterior insular cortex (AI) is critical for processing of social rejection. The present study expands on this conceptualization, by showing that these areas are involved in processing of self-relevant social evaluation, irrespective of valence. Forty healthy adolescents (N = 20 females) were tested in a magnetic resonance imaging (MRI) scanner. We used a novel paradigm that balanced participants’ experience of rejection and acceptance. In addition, the paradigm also controlled for whether the social judgment was towards the participants or towards other fictitious players. By creating a “self” and “other” distinction, we show that right AI and dACC are involved in processing the salience of being judged by others, irrespective of the quality of this judgment. This finding supports the idea that these regions are not specific to social rejection or even to pain or metaphorically painful experiences, but activate to self-relevant, highly salient information.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (www.psymri.com). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

ObjectiveOne major issue in dynamic susceptibility contrast MRI (DSC-MRI) is to accurately determine contrast agent (CA) concentration, since T2* relaxivity in vivo is generally unknown and varies between blood and tissue. In this study, quantitative susceptibility mapping (QSM) was used for quantification of CA concentration.Materials and methodsA DSC-MRI protocol, including phase data acquisition, was applied to 20 healthy volunteers in a test–retest study. By selecting a CSF reference region of interest (ROI), the values of all QSM images were shifted to show no CA-induced change in CSF. CA concentration and cerebral blood volume (CBV) were estimated using shifted QSM data. CSF reference ROI optimization was evaluated by investigation of CBV repeatability. The CBV age dependence was analysed and tissue T2* relaxivity was estimated.ResultsThe best repeatability of CBV, using an optimal CSF reference ROI, showed test-versus-retest correlations of r = 0.81 and r = 0.91 for white and grey matter, respectively. A slight CBV decrease with age was observed, and the estimated in vivo T2* relaxivity was 85 mM−1s−1.ConclusionProvided that a carefully selected CSF reference ROI is used to shift QSM image values, susceptibility information can be used to estimate concentration of contrast agent and to calculate CBV.Electronic supplementary materialThe online version of this article (doi:10.1007/s10334-017-0637-9) contains supplementary material, which is available to authorized users.

Background: Interpersonal stress and perceived rejection have been clinically observed as common triggers of nonsuicidal self-injury (NSSI), with self-injury behavior regulating both affective and social experiences. We investigated whether the subjective interpretation of social interaction in a simulated online environment might be biased in the NSSI group, and the brain mechanisms underlying the experience. Methods: Thirty female adolescent patients with NSSI and thirty female age-matched controls were investigated in this case-control study. In our novel task that simulates interaction on current social media platforms, participants indicated whether they liked or disliked pictures of other players during a functional magnetic resonance imaging (fMRI) scan. Participants also viewed positive and negative feedback directed toward them by others. The task also assessed the subjective effects of the social interaction. Finally, subjects underwent a separate facial electromyography session, which measured facial expressions processing. Outcomes: Behaviorally, the NSSI group showed a negative bias in processing social feedback from others. A multi-voxel pattern analysis (MVPA) identified brain regions that robustly classified NSSI subjects and controls. Regions in which mutual activity contributed to the classification included dorsomedial prefrontal cortex and subgenual anterior cingulate cortex, a region implicated in mood control. In the NSSI group, multi-voxel classification scores correlated with behavioral sensitivity to negative feedback from others. Results remained significant after controlling for medication, symptoms of depression, and symptoms of borderline personality disorder. Interpretation: This study identified behavioral and neural signatures of adolescents with NSSI during social interaction in a simulated social media environment. These findings highlight the importance of understanding social information processing in this clinical population and can potentially advance treatment approaches.